Chemokines regulate the trafficking of various types of mononuclear cells. They are classified into four subfamilies of CC, CXC, CX3C, and C, based on positions of conserved cysteine residues in their N-termini.
Stromal-derived factor-1 (SDF-1), a CXC chemokine, plays key roles in homing and mobilization of hematopoietic stem cells, endothelial progenitor cells, and hematopoietic progenitor cells. The physiological function of SDF-1 is mediated by the type 4 CXC chemokine receptor (CXCR4).
The interaction between CXCR4 and SDF-1 contributes to multiple pathological conditions such as HIV, rheumatoid arthritis, asthma, and tumor metastases. For example, activation of the CXCR4/SDF-1 pathway in tumors leads to upregulation of angiogenic vascular endothelial growth factor (VEGF). On the other hand, disrupting the interaction between CXCR4 and SDF-1 by CXCR4 antagonists suppresses VEGF-dependent tumor angiogenesis and growth. Compounds that disrupt the interaction between CXCR4 and SDF-1 can be used for treating various diseases including tissue injury, cancer, inflammatory disease, and autoimmune disease.
There is a need to develop new compounds that can effectively disrupt the interaction between CXCR4 and SDF-1.